Lipids

The term lipid describes a group of biological compounds that are insoluble
in water but are relatively soluble in many organic solvents. Thus, unlike the
other major groups of biological molecules--proteins,
carbohydrates, and nucleic acids--lipids are
categorized by a physical property rather than by structural features.

CLASSIFICATION

Lipids can be classified in three subgroups based on chemical composition:
hydrocarbons, simple lipids, and complex lipids. Hydrocarbons contain carbon and
hydrogen only. Simple lipids contain C, H, and O, and complex lipids contain one
or more additional elements, such as phosphorus,
nitrogen, or sulfur.

Simple Lipids

Simple lipids can be segregated into structural types, which are
fatty acids (FA), waxes, triglycerides (TG), and
sterols. A fatty acid is a long-chain monocarboxylic acid, and a wax is the
ester of a long-chain alcohol and a fatty acid. A triglyceride is the ester of a
glycerol that contains three FA molecules. sterols are a special class of
alcohols, containing a fused four-ring structure, or steroid nucleus. Sterols
may combine with a fatty acid to form sterol esters.

Complex Lipids

Among the complex lipids, important structural types are phosphoglycerides,
phosphosphingolipids, and glycolipids. The parent phosphoglyceride, phosphatidic
acid (PA), is similar in structure to a triglyceride except that the 3-hydroxyl
group of the glycerol component is esterified to phosphoric acid rather than to
FA.

Further esterification of the phosphoric acid of PA with a variety of small,
hydroxyl-containing molecules leads to a series of derived phosphoglycerides,
including phosphatidyl choline (PC), commonly known as lecithin, phosphatidyl
ethanolamine (PE), and phosphatidyl serine (PS).

The phosphosphingolipids are derived from sphingosine, a long-chain
dialcohol with an amino group. The formation of an amide with an FA at one point
along this chain yields ceramide. Esterification of a ceramide derivative with
phosphorylcholine yields sphingomyelin, which is the major phospho-sphingolipid.
If ceramide is instead linked to a simple sugar, a cerebroside glycolipid is
formed. Further addition of several amino sugars yields the lipids called
gangliosides.

DISTRIBUTION AND FUNCTION

Lipids are found in all organisms as structural components of the cell
membrane. In most animals the major membrane lipids are lecithin, PE, PS, and a
sterol, cholesterol. Cell membranes of the central nervous system contain, in
addition to the above, sphingomyelin, myelin, cerebrosides, and gangliosides. In
higher plant membranes, lecithin and PE predominate, although phosphatidyl
glycerol (PG) and phosphatidyl inositol (PI) are also present.
Cholesterol is absent, but other sterols, known
as phytosterols, are commonly present. Bacterial membranes are unique in that
lecithin is rarely present and sterols are completely absent; PE and PG are
usually the major lipids.

Although triglycerides are not important membrane lipids, they are stored in
most animals and plants as a metabolic energy reserve (see metabolism). In
vertebrates, TG is located in adipose (fat) tissue, which is widely distributed
in the body. In insects, TG is concentrated in a specific fat body that
functions both as a depot and as a center for triglyceride metabolism. In higher
plants, TG is found in the seeds of most plants and is the source of most
vegetable oils. In a few plants, such as the avocado, the palm, and the olive,
the fruit also contains large amounts of triglycerides.

Lipids have a number of specialized functions. In mammals living in cold
climates, subcutaneous fat retards loss of body heat. Hydrocarbons and waxes on
insect cuticle, as well as on plant leaves and fruit, aid in water retention.
Certain cyclic FA, the prostaglandins, are involved in blood clotting and
hormonal responses in mammals, and a variety of other FA derivatives serve as
sex attractants and growth regulators in insects. sex hormones and the adrenal
corticoids of higher animals are lipids derived from cholesterol. Essential
dietary lipids include certain polyunsaturated fatty
acids as well as the vitamins A,
D, E, and
K.

METABOLISM

Triglycerides supply 30 to 50 percent of the calories of the average
American diet. Ingested TG is hydrolyzed in the gut and absorbed as fatty acid
and monoglyceride. Resynthesis of TG takes place within the intestinal cells and
appears first in lymph and then in blood as the major component of chylomicrons,
lipoproteins secreted by intestinal cells, which transport dietary lipid to
adipose tissue and liver.

Lipid manufactured in the liver, chiefly from carbohydrates,
is transported in the blood by three other lipoproteins that are named according
to their behavior in an ultracentrifuge: extremely low-density lipoproteins
(VLDL), involved in TG transport, low-density lipoproteins (LDL) for cholesterol
transport, and high-density lipoproteins (HDL), the carriers of
phosphoglycerides and cholesterol. In the capillaries of adipose tissue, the TG
of chylomicrons and VLDL are hydrolyzed to glycerol and FA. The FA is taken up
by adipose cells and again converted to TG for deposition. At the same time, TG
within the cells is hydrolyzed and released into the blood as FA and transported
to other tissues for oxidation. The heart, for example, normally obtains 70
percent of its metabolic energy by this process.

In order to produce energy, FA is first degraded into acetate units by a
process known as oxidation, which is carried out in mitochondria. Acetate, in
turn, is oxidized to carbon dioxide by means of enzymes of the citric acid
cycle, also known as the Krebs cycle, resulting in the manufacture of the
high-energy molecule adenosine triphosphate (ATP). The basic building blocks for
triglyceride synthesis, acetate and glycerol-3-phosphate (GP) can be derived
from either carbohydrate or
amino acid metabolism. Thus even in a fat-free
diet, a caloric intake in excess of that needed for metabolic energy leads to a
net increase of lipid in adipose tissue.

In higher animals, the liver is the major site of fatty
acid synthesis. FA, synthesized from acetate, combines with GP to yield
phosphatidic acid. After enzymatic removal of the phosphate group of
phosphatidic acid, the resulting diglyceride combines with another FA to yield
triglycerides. The liver can then release these triglycerides into the blood as
VLDL for transport to adipose tissue. Acetate is also the precursor for
cholesterol synthesis, whereas phosphatidic acid is the direct precursor of the
phosphoglycerides.